In response to RFA-AA-12-006, this application proposes the SRI International Research Component of the National Consortium on Alcohol and Neurodevelopment in Adolescence (N-CANDA) to determine the effects of alcohol use on the developing adolescent brain. Recruited at ages 12 through 21, a high risk enhanced community sample of 170 SRI subjects (N=680 from all sites) will complete a baseline assessment and undergo three annual follow-up assessments in an accelerated longitudinal design. At each visit, a multimodal magnetic resonance imaging (MRI) protocol, comprehensive neuropsychological battery, and assessments of alcohol and other substance use and related problems, mental health symptomatology, and substance use disorder risk factors will be measured. Brain imaging includes state-of-the-art high resolution structural MRI (sMRI), diffusion tensor imaging (DTI), and resting state MRI (rsMRI). The examination of alcohol consequences will focus on structural and functional maturation of brain areas that are actively developing during adolescence, involved in psychological regulation, responsive to rewards, and thought to be vulnerable to untoward alcohol effects. In addition, the SRI Research Component will collaborate on two additional studies. We will collaborate with Pittsburgh in a laboratory sleep study to examine the effects of adolescent heavy drinking on developmental trajectories of sleep EEG, a novel and sensitive marker of functional brain integrity. We will also collaborate with UCSD to study the effects of adolescent heavy drinking on default mode network integrity, and the extent to which this mediates cognitive performance, using functional connectivity analysis of data acquired in an fMRI protocol conducted during a Stroop Match-to-Sample Task. Studied in the context of risks and baseline brain characteristics, we will determine both the effects of alcohol exposure on the developmental trajectory of the adolescent human brain, and identify preexisting psychobiological vulnerabilities that may put an adolescent at heightened risk for an alcohol use disorder. PUBLIC HEALTH RELEVANCE: Successful completion of the above aims will demonstrate that adolescent alcohol involvement disrupts brain development. This project represents a critical step in understanding neurobiological risks for accelerated alcohol use and alcohol effects on brain development in adolescence.